Drug fails to prevent cancer

Sulindac, and anti-inflammatory drug that, in preliminary research, looked promising for preventing cancer in children, turned out to be ineffective according to a recent study.

"Prior studies indicated that sulindac can reduce polyps in older, symptomatic patients, but it was unknown whether it could prevent polyps in patients who hadn't developed any polyps yet," said Dr. Francis M. Giardiello of the Kimmel Cancer Center at Johns Hopkins University, "unfortunately, our study says the answer is no."

Anti-inflammatory drugs such as sulindac were initially reported to help prevent a form of hereditary colon cancer by blocking the tumor's growth in the pre-cancerous stage in young children. Initial studies showed that the anti-inflammatory drugs could hold off pre-cancerous polyps in the colons of patients that already have them as a part of the disease adenomatous polyposis.

The drug were tested as a part of a four-year experiment in which patients who were genetically destined to develop the disease were given sulindac and the rate of polyp formations was recorded. Nine of 21 patients who were given the drug developed polyps, which is not statistically different from the placebo group, of which 10 of 20 developed cancer.

The genetic test for adenomatous polyposis was developed by researchers at Hopkins several years ago. This test helps doctors identify if patients that have a family history of the disease are susceptible.

Giardiello said that "despite prior evidence that sulindac is effective in older patients who already have symptoms, we found no statistical difference between the two groups (who did or did not get the drug) in thwarting the development of polyps or subsequent colon cancer."

Giardiello still believes that "the door is still open." He thought it possible that increasing the dose would be effective.

Sulindac is normally used as an anti-inflammatory drug to ease the pain of arthritis and similar ailments. It works by blocking the enzymes responsible for the body's normal inflammation response. The primary enzyme which sulindac targets is prostaglandin.

"We know that NSAIDs inhibit prostaglandin levels," Giardiello says. "We found that those persons who developed polyps had higher levels of prostaglandins, so some patients might metabolize the drug differently."

Polyps begin growing in the colons of patients with adenomatous polyposis by about age 15, and by age 30 they begin to turn cancerous. Currently, the only available treatment method for the disease is to remove the colon entirely, a procedure which has moderate risk and causes severe discomfort for the patient.

Two British cancer specialists, Ian Chau and Dr. David Cunningham, commented in a journal editorial that while the Hopkins study is "relatively disappointing" they still feel that anti-inflammatory drugs "may yet be shown to have a role in the primary prevention or treatment of established colorectal cancer."

Dr. Bernard Levin, Vice-President for Cancer Prevention at the M.D. Anderson Cancer Center at the University of Texas believes that there may have been other reasons for the drug's failure.

"The dose may have been inadequate," he says. "The compound itself may be insufficiently powerful to affect a change in people who are genetically predisposed. Perhaps a combination of medications are needed to overcome the genetic drive."

"I don't think the premise is disproved by this study," says Levin. "What it tells us is that FAP is a very tough nut to crack, and that surgery still is the choice. Obviously, this field is a work in progress. It will take years to tell whether single agents or a combination are effective."

Giardiello is currently working on a clinical trial that is testing the effectiveness of several other NSAIDS such as, celecoxib, sold commercially as Celebrex, which is part of a family of drugs called cox-2 inhibitors.

"Higher doses of the drugs might work, a combination of drugs might work," says Giardiello. "The story is still ongoing.